Histopathological assessment of infected tissues revealed a large number of syncytia within the lymphoid tissue from days 5—7 post infection. In the later stage of infection erosive lesions are formed in the oral cavity that also become necrotic. The severity of clinical signs generally peaks between 6 and 8 days post infection and can continue for up to 14 days leading to death or recovery from infection.
Despite the segregation of isolates of Peste des petits ruminants virus into lineages, the early stages of pathogenesis in goats infected with virulent strains of the virus had no lineage specific difference in the pathogenicity of the virus Baron et al. Immunohistochemical staining of Peste des petits ruminants virus antigen in experimentally infected goats. Adapted from Pope et al. Peste des petits ruminants virus is highly lymphotropic and infection often leads to a profound immunosuppression that causes leucopoenia and reduced antibody responses Pope et al.
Immunosupression by Peste des petits ruminants virus has been observed in both vaccinated and infected animals Rajak et al. Virulent strains of the virus cause marked immunosuppression, whereas vaccination only induces a transient leucopoenia with no significant effects on the immune response Rajak et al. Leucopoenia is observed generally from the fourth day post-infection and may revert depending on progression of disease Pope et al. Maternal antibodies against the virus can be detected in young animals and remain able to neutralise virus for three to four months enabling a level of protection in newborn animals Libeau et al.
Therefore, vaccination of new born animals is not necessary until that age Bodjo et al. Cellular and humoral immune responses are induced upon infection or vaccination, a feature of the live attenuated vaccines available for the virus. An inflammatory response in goats infected with different strains of the virus was observed with the enhanced expression of cytokines Atmaca and Kul, , Baron et al.
Morbillivirus non-structural proteins have been shown to play a role in the blocking of type I and type II interferon action Ohno et al. Cell-mediated and humoral immune responses against the virus are mainly directed against the H, F and N proteins Sinnathamby et al. Both cytotoxic B cell and T cell epitopes have been mapped to regions on the N protein Mitra-Kaushik et al.
B cell epitopes have also been mapped to the H protein of the virus Renukaradhya et al. Peste des petits ruminants can be confused with other diseases including rinderpest, bluetongue and contagious caprine pleuropneumonia, due to the similarity of these diseases in clinical signs.
Diagnosis of the disease may also be complicated, as the result of secondary bacterial infections specifically caused by Mannheimia haemolytica.
Therefore, in addition to clinical observations, a differential diagnosis must be confirmed by laboratory diagnostic techniques. The laboratory tests currently available for diagnosis of the disease can be grouped into three categories: i those detecting virus or viral antigen e.
The available laboratory test methods for diagnosis of the disease are summarised in Table 6. However, the efficiency of laboratory diagnosis can be greatly influenced by the integrity of the sample received, often affected by the conditions of its by collection and transportation.
Finally, an immunochromatographic lateral flow device has been developed as a pen-side test using a monoclonal antibody, specific to the virus H protein Bruning-Richardson et al. This test has recently been validated under field conditions for diagnosis as early as 4 days post-infection, before onset of severe clinical signs Baron et al.
Preventive measures employed in disease free areas include strict restrictions on the importation of animals from disease infected regions. Disease can be efficiently controlled by isolation and slaughtering of infected animals, as well as disinfection of environmental materials and the restriction of animal movements.
Immunisation can be performed with commercially available attenuated vaccines that elicit a protective immunity that has been shown to be effective for at least three years post-vaccination Diallo et al. Current vaccination schedules require the immunisation of susceptible animals at least every three years Diallo et al. Vaccination in animals aged 4—6-months is recommended Balamurugan et al.
This is an important area in the control programmes of the disease, as introduction of unvaccinated animals into a potentially susceptible population can lead to introduction of the virus into a farm and can cause a fresh outbreak of disease.
Currently available vaccines require maintenance of the cold chain to ensure maintenance of maximal virus titre for inoculation and the required serological response to vaccination. Tissue culture rinderpest vaccine TCRV used as a heterologous vaccine against peste des petits ruminants was found to be effective, due to the antigenic relatedness between these two ruminant morbilliviruses Mariner et al.
However, use of this vaccine was prohibited in , due to the lack of DIVA following vaccination and the need for extensive serological monitoring during the final stages of the rinderpest eradication campaign.
In an initial attempt to generate a homologous vaccine, Peste des petits ruminants virus was grown on primary cell line of sheep liver cells Gilbert and Monnier, , but after 65 serial passages in primary cell culture, the virus was not sufficiently attenuated Benazet, Later, Diallo et al. Following 63 passages the virus was deemed suitably attenuated following extensive in vivo studies Diallo et al. Similarly, at least three more vaccine strains, specifically Sungri 96, Arasur 87 and Coimbatore 97, have been developed for use as vaccines following 75 serial passages in Vero cells Singh et al.
These attenuated vaccines are now available in freeze-dried form and include various chemical stabilisers to reduce the thermolability of the virus and reduce the need for the cold chain Mariner et al. Subunit vaccines for morbilliviruses have been developed for several species.
Initial work carried out with Capripox virus strains expressing F and H proteins of Rinderpest virus were shown to protect goats against Peste des petits ruminants virus Romero et al. Capripox virus strains expressing the homologous Peste des petits ruminants virus H Diallo et al.
Concerns regarding efficacy of recombinant bivalent Capripox virus and Peste des petits ruminants virus vaccine F and H proteins in sheep or goats with pre-existing immunity against either of the viruses have been addressed recently Caufour et al. Animals with pre-existing immunity for either virus, achieved by immunising animals with a single-type vaccine, were inoculated with the bivalent vaccine and after four weeks were challenged with a virulent Capripox virus strain followed by a virulent Peste des petits ruminants virus strains after another three weeks.
In all cases, complete protection against Capripox virus was evident; however, partial protection against Peste des petits ruminants virus was detected in animals previously immunised against Capripox virus. This indicated a limited replication of the Capripox -PPRV F and H bivalent vaccine in the presence of pre-existing antibodies against the virus, which led to a poor expression of the Peste des petits ruminants virus F and H proteins and, therefore, reduced the level of antibody response against the latter virus.
The vaccinia virus vector Modified vaccinia Ankara expressing Peste des petits ruminants virus F and H proteins was shown to protect goats against the disease after the administration of two doses of the vaccine Chandran et al. Goats immunised with a vaccine containing recombinant fowl pox virus expressing the H or F proteins of Peste des petits ruminants virus had a poor antibody response to the heterologous proteins Herbert et al.
Recombinant adenovirus vectors expressing glycoproteins of the virus have also been developed Qin et al. The recombinant replication-defective Human adenovirus serotype 5 incorporating H or F proteins of Peste des petits ruminants virus was shown to induce humoral and cell mediated immunity and protected goats Herbert et al.
These vaccines need to be tested further in large scale studies to assess their potency and, more importantly, the duration of immunity in comparison to the conventional live attenuated vaccines, as vaccinated animals are exposed to only one or two proteins of the virus. Subunit vaccines have also been developed based on Baculovirus expression systems expressing the H Sinnathamby et al. However, these need to be evaluated further for safety and efficacy.
Similarly, such assessments are required for DNA vaccines Yang et al. Many small ruminant diseases, e. A vaccination programme with increased valency that is able to generate neutralising responses to several disease following a single administration would improve the efficiency of control programmes and reduce costs associated with such a programme. Live bivalent vaccines against goat pox and peste des petits ruminants Rajak et al.
The need for the further development of vaccines against peste des petits ruminants revolves around three approaches: i the development of thermostable vaccine preparations to overcome the costly requirement of cold chain maintenance, ii the fulfilment of DIVA principles to enable effective post vaccination seromonitoring and iii the production of multivalent vaccines that could induce neutralising responses against several diseases alongside peste des petits ruminants.
Whilst only thermostable preparations are primarily required to control the disease, vaccines that could fulfil the other two approaches would significantly reduce costs associated with vaccination, which is a significant issue in regions where the disease is endemic. Reverse genetics techniques are being investigated to address the DIVA issue in the preparation of relevant vaccines.
The new genome cDNA can then be manipulated to obtain the modified form of the virus. Use of reverse genetics techniques to negatively or positively tag vaccines Hu et al.
Recently, positively or negatively marked vaccines Fig. In a negatively marked vaccine, the epitope binding site of the C77 monoclonal antibody, the monoclonal antibody used to compete against antibodies in test sera in the competitive H ELISA, was removed by epitope deletion.
However, although the C77 mAb was unable to bind to the mutated form of H protein in in vitro tests, the mutation was not sufficient to enable DIVA under field conditions, hence further alterations to the proposed epitope within H are being investigated. Adapted from Muniraju et al. For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.
Peste des petits ruminants affects some of the poorest farming communities on the planet and presents a significant barrier to development and sustainability of small ruminant farming.
The successful eradication of rinderpest has led the attention of the scientific community to peste des petits ruminants as a further potential target for global eradication. In a recent meeting, the World Organisation for Animal Health and the Food and Agriculture Organisation have proposed a control programme for the disease with the target year for eradication being FAO, However, the scientific and economic infrastructures present in areas where the disease is endemic, are largely insufficient to mount a viable eradication campaign without international aid.
The recent emergence of the disease across China has highlighted the ability of the virus to spread rapidly across vast areas causing significant economic losses Banyard et al. The vaccines currently available to protect small ruminants against the virus are sufficient to enable an eradication campaign, although there is little doubt that refinements to vaccines would reduce the costs associated with control, making eradication in areas with limited resources more readily achievable.
Recent advances in the generation of recombinant versions of the virus will serve as suitable starting points for development of novel vaccine formulations Hu et al. The current understanding of disease pathogenesis and mechanisms of virulence require further expansion that will have ramifications on the knowledge of Peste des petits ruminants virus and related viruses of both veterinary and medical importance. Assessment of genetic data is starting to unravel elements of the evolutionary biology behind Peste des petits ruminants virus and its relationship with other morbilliviruses Muniraju et al.
The detection and genetic characterisation of novel morbilliviruses from different species may indicate further approaches for the control and eradication of these important viral pathogens. National Center for Biotechnology Information , U. Sponsored Document from.
Vet Microbiol. Muniraju , a M. Mahapatra , a D. Muthuchelvan , c H. Buczkowski , d and A. Banyard d. Author information Copyright and License information Disclaimer. Parida: ku. This article has been cited by other articles in PMC. Abstract Peste des petits ruminants virus causes a highly infectious disease of small ruminants that is endemic across Africa, the Middle East and large regions of Asia. Taxonomy of the causative virus Peste des petits ruminants virus belongs to genus Morbillivirus , sub-family Paramyxovirinae , family Paramyxoviridae , and order Mononegavirales, alongside other important viral pathogens, e.
Table 1 Classification of viruses within the order Mononegavirales. Open in a separate window. Characteristics of the causative virus 3. Virion morphology and genome structure Structurally, morbilivirus virions are visualised as pleomorphic, enveloped particles as determined using negative-stain electron microscopy.
Table 2 Genome organisation of the Peste des petits ruminants virus. Virus replication cycle The replication cycle for different paramyxoviruses is similar and the first step is the attachment of the virus on the cell surface and membrane fusion to release a genome into the cell cytoplasm Fig.
Epidemiological characteristics 4. NA: not available. Host range Sheep and goats are the primary hosts for Peste des petits ruminants virus with few reports of disease outbreak in camels Roger et al. Table 5 Reported infection of wildlife species by Peste des petits ruminants virus. Disease processes 5. Clinical signs Although goats and sheep are the primary hosts for the virus, goats seem to be more susceptible to disease than sheep Nanda et al.
Pathogenesis Disease progresses with development of lacrimal, nasal and mucosal discharges and viral material can be detected in such excretions as early as 4 days after infection.
Immunosuppression Peste des petits ruminants virus is highly lymphotropic and infection often leads to a profound immunosuppression that causes leucopoenia and reduced antibody responses Pope et al. Immunological features Maternal antibodies against the virus can be detected in young animals and remain able to neutralise virus for three to four months enabling a level of protection in newborn animals Libeau et al.
Disease diagnosis Peste des petits ruminants can be confused with other diseases including rinderpest, bluetongue and contagious caprine pleuropneumonia, due to the similarity of these diseases in clinical signs.
Table 6 Laboratory methods available for the diagnosis of peste des petits ruminants. Control Preventive measures employed in disease free areas include strict restrictions on the importation of animals from disease infected regions. Attenuated vaccines Tissue culture rinderpest vaccine TCRV used as a heterologous vaccine against peste des petits ruminants was found to be effective, due to the antigenic relatedness between these two ruminant morbilliviruses Mariner et al.
Table 7 Characteristics of attenuated vaccines against peste des petits ruminants. Recombinant subunit vaccines Subunit vaccines for morbilliviruses have been developed for several species. Improvement of existing attenuated vaccines Many small ruminant diseases, e. Concluding remarks Peste des petits ruminants affects some of the poorest farming communities on the planet and presents a significant barrier to development and sustainability of small ruminant farming.
Conflict of interest statement Authors have no conflict of interest. References Abd El-Rahim I. An outbreak of peste des petits ruminants in migratory flocks of sheep and goats in Egypt in Abu Elzein E.
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In epidemic form, it was the most lethal plague known in cattle. All wild and domesticated species of the order Artiodactyla were variably susceptible to rinderpest, although dissemination of the virus largely depended on continual transmission among domesticated cattle, buffalo, and yaks.
The virus also infected goats and sheep, leading to underdiagnosis of the clinically similar peste des petits ruminants in regions where the two diseases coexisted. Rinderpest virus is a Morbillivirus , closely related to the viruses causing peste des petits ruminants, canine distemper Canine Distemper read more , and measles. Strains of varying virulence for cattle occurred and could be differentiated genetically.
However, a single serotype of the virus existed, and a vaccine prepared from any strain could protect against all strains. Rinderpest virus is shed in nasal and ocular secretions and can be transmitted during the incubation period 1—2 days before onset of fever. Transmission required direct or close indirect contact between susceptible animals and sick animals shedding the virus. The role of fomites in transmission was negligible, because the virus is fragile, being inactivated within 12 hours of exposure to atmospheric heat and light.
There was no carrier state, and recovered animals acquired lifelong immunity. In endemic areas, young cattle became infected after maternal immunity disappeared and before vaccinal immunity began, with possible auxiliary cycles in wild ungulates.
After an incubation period of 3—15 days, fever, anorexia, depression, and oculonasal discharges developed, followed by necrotic lesions on the gums, buccal mucosa, and tongue. The hard and soft palates were often affected. The oculonasal discharge became mucopurulent, and the muzzle appeared dry and cracked. Diarrhea, the final clinical sign, could be watery and bloody. Convalescence was prolonged and could be complicated by concurrent infections due to immunosuppression.
Histologic lesions included lymphoid and epithelial necrosis with viral-induced syncytia, and intracytoplasmic and intranuclear inclusions were often seen. It is recommended that post-eradication laboratory diagnosis of rinderpest focus on molecular techniques such as RT-PCR , which are not only accurate but also allow for phylogenetic analysis to pinpoint the source of any re-emerging virus strain. Clinical and pathologic findings were sufficient for diagnosis of rinderpest in endemic areas and after initial laboratory confirmation of an outbreak.
In areas where rinderpest was uncommon or absent, laboratory tests had to be used to differentiate it from bovine viral diarrhea in particular, as well as East Coast fever, foot-and-mouth disease, infectious bovine rhinotracheitis, and malignant catarrhal fever. Virus isolation and detection of specific viral antigens in affected tissues using an immunodiffusion test was the standard, but simpler, more rapid and more discriminating tests, such as antigen-capture ELISA and reverse transcription PCR RT-PCR , were favored toward the end of the eradication campaign.
With regard to the last case and as an alternative viral vector, a BoHVbased vector platform was employed in the present work to deliver and express PPRV-H gene in transduced cells of immunocompetent mice as surrogate animal model. Although no murine model for PPRV induced disease exists, they represent an invaluable model to initially test the immunity induced by new prototype vaccines.
The direct use of large animals could represent a major waste of resources, in terms of maintenance and biosafety containment structures, especially in the event of experiment failure. Data provided by immunized mice not only can be obtained quickly and cheaply but also they could represent a predictive and orientative tool of the vaccine immunogenicity in the natural host, e. PPRV-H protein possesses both hemagglutinin and neuraminidase activities and has a hydrophobic domain at the N-terminus amino acid position 35—38 , which remains within the mature protein acting as a signal peptide that anchors the protein into the membrane BoHV-4 has no clear direct disease association; however, its pathogenic potential cannot be absolutely excluded.
This is an important consideration since it is to be used as a gene delivery vector. In fact, BoHV-4 has been often associated with postpartum metritis in cattle along with specific endometotropic 39 , Importantly, BoHVA-based vector behaves like a replicating incompetent viral vector in both wild-type and immunocompromised mice, showing complete absence of pathogenicity 16 , 17 , 19 , 27 , 44 , The derived replication-deficient recombinant vector could transduce mammalian cells and expressed PPRV-H protein.
This construct could therefore potentially elicit immunity to the transgene. Relevant planning will however be needed before this recombinant vector can legally be licensed for employment in the field. Protective natural immunity to morbilliviruses requires both humoral and cellular components of the adaptive immune system. Humoral immunity can protect against the prototype morbillivirus measles virus re-infection, whereas cellular immunity controls virus clearance and dissemination 46 , This recombinant vector vaccine can therefore potentially stimulate the T cell immunity essential for virus clearance.
It was previously shown that a neutralization titer higher than 10 correlates with a long-lasting humoral response and could be considered as a successful vaccination and protection indicator in the field 48 , In this pilot study, the lowest VNA titer obtained for all vaccinated mice was never below This is further supported by the fact that BoHV-4 has been successfully used in sheep and goats 13 , BoHVbased vector delivering H alone also induced neutralization titers higher than those obtained with other viral vectors delivering both H and F antigens, which is in line with the concept that H glycoprotein of Paramyxovirus is a stronger inducer of VNA than the F glycoprotein 50 , Despite the notion that antibody immune response against PPRV is the main factor for an efficient protection, cellular immune response can be also important for virus clearance.
In some cases, protection has been obtained even with undetectable level of VNA titers 52 , GD conceived the experiments. GD wrote the paper. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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